Discovery of 2-substituted benzoxazole carboxamides as 5-HT3 receptor antagonists
The discovery of a novel series of benzoxazole-4-carboxamides is described. A structure–activity relationship study resulted in the identification of 2-amino benzoxazoles 41 and 48 as selective, orally bioavailable 5-HT3 receptor antagonists. A new class of 2-substituted benzoxazole carboxamides are...
Saved in:
Published in | Bioorganic & medicinal chemistry letters Vol. 20; no. 22; pp. 6538 - 6541 |
---|---|
Main Authors | , , , , , , , , , , , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Amsterdam
Elsevier Ltd
15.11.2010
Elsevier |
Subjects | |
Online Access | Get full text |
Cover
Loading…
Summary: | The discovery of a novel series of benzoxazole-4-carboxamides is described. A structure–activity relationship study resulted in the identification of 2-amino benzoxazoles 41 and 48 as selective, orally bioavailable 5-HT3 receptor antagonists.
A new class of 2-substituted benzoxazole carboxamides are presented as potent functional 5-HT3 receptor antagonists. The chemical series possesses nanomolar in vitro activity against human 5-HT3A receptors. A chemistry optimization program was conducted and identified 2-aminobenzoxazoles as orally active 5-HT3 receptor antagonists with good metabolic stability. These novel analogues possess drug-like characteristics and have potential utility for the treatment of diseases attributable to improper 5-HT3 receptor function, especially diarrhea predominant irritable bowel syndrome (IBS-D). |
---|---|
Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0960-894X 1464-3405 |
DOI: | 10.1016/j.bmcl.2010.09.038 |